Our objective is to determine the pathogenesis of cardiac abnormalities in heart muscle as a consequence of diabetes mellitus and the influence of several types of interventions on these abnormalities. Our goals include the evaluation of the influence of physical conditioning on the electrical and mechanical properties of the heart in a canine model of diabetes. Since the response of the diabetic heart to acute ischemia is controversial and partial occlusion of a coronary artery is common in human pathology, we have initially examined the response of nondiabetic normals to acute subendocardial ischemia in terms of cardiac function, as well as the redistribution of water and electrolytes in the intracellular compartment of the ischemic myocardium. The effects of enhancing glucose uptake during ischemia with acetylsalicylate have also been investigated. As an approach to the question of the significance of the occlusive disease in the intramural coronary arteries that allegedly occurs in diabetics, we have examined the heart noninvasively in patients with sickle cell anemia since the process of crisis is thought to involve acute occlusion of the small intramyocardial vessels by sickled red cells. Finally, the systolic time interval method has been used to asses the relationship of abnormalities in asymptomatic diabetics to fasting blood glucose and progression with time.